title: Derivation of an aquatic predicted no-effect concentration for the synthetic hormone, 17 alpha-ethinyl estradiol.
abstract: 17alpha-Ethinyl estradiol (EE2) is a synthetic estrogen widely used in combination with other steroid hormones in oral contraceptives and in the contraceptive patch. EE2 has been detected in sewage treatment plant effluents in the low nanogram -per-liter range and occasionally in surface waters in the U.S., U.K., Canada, Brazil, Germany, and elsewhere. The mode of action is receptor-mediated, and estrogen receptors exist in mammals and other vertebrates. A large number of studies on the effects of EE2 on aquatic organisms exist. One hundred English language studies published between 1994 and 2007, one as yet unpublished study, and findings published in conference proceedings (in German) were compared to published data quality criteria to identify the most relevant studies for deriving a predicted no-effect concentration (PNEC). Reproduction in fish was identified as the most sensitive end point in aquatic species. A species sensitivity distribution was constructed using no observed effect concentrations (NOECs) for reproductive effects from 39 papers in 26 species, resulting in a median hazardous concentration at which 5% of the species tested are affected (HC5,50) of 0.35 ng/L. After comparing this HC5,50 to all of the laboratory and field-derived toxicity information available for EE2, we recommend using 0.35 ng/L as the PNEC for EE2 in surface water. This PNEC is below 95% of the existing NOECs for effects on reproduction and is also below virtually all of the NOECs for vitellogenin induction in the key fish reproduction studies.
authors.affiliation: Johnson & Johnson, New Brunswick, New Jersey, USA. dcaldwel@its.jnj.com
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Caldwell
authors.forename: Frank
authors.initials: F
authors.lastname: Mastrocco
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Hutchinson
authors.forename: Reinhard
authors.initials: R
authors.lastname: Länge
authors.forename: Dagobert
authors.initials: D
authors.lastname: Heijerick
authors.forename: Colin
authors.initials: C
authors.lastname: Janssen
authors.forename: Paul D
authors.initials: PD
authors.lastname: Anderson
authors.forename: John P
authors.initials: JP
authors.lastname: Sumpter
mesh_terms: D000818:Animals; D004777:Environment; D004997:Ethinyl Estradiol / Q000633:toxicity*; D005399:Fishes / Q000254:growth & development / Q000502:physiology*; D008018:Life Cycle Stages / Q000187:drug effects; D019055:No-Observed-Adverse-Effect Level; D011157:Population Dynamics; D012098:Reproduction / Q000187:drug effects; D013045:Species Specificity; D014819:Vitellogenins / Q000378:metabolism
chemical_list: D014819:Vitellogenins; D004997:Ethinyl Estradiol